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ObjectiveSleep disturbances are associated with increased risk of migraine, however the extent of shared underlying biology and the direction of causal relationships between these traits is unclear. Delineating causality between sleep patterns and migraine may offer new pathophysiologic insights and inform subsequent intervention studies. Here, we used genetic approaches to test for shared genetic influences between sleep patterns and migraine, and to test whether habitual sleep patterns may be causal risk factors for migraine and vice versa.MethodsTo quantify genetic overlap, we performed genome-wide genetic correlation analyses using genome-wide association studies of nine sleep traits in the UK Biobank (n ≥ 237,627), and migraine from the International Headache Genetics Consortium (59,674 cases and 316,078 controls). We then tested for potential causal effects between sleep traits and migraine using bidirectional, two-sample Mendelian randomization.ResultsSeven sleep traits demonstrated genetic overlap with migraine, including insomnia symptoms (rg = 0.29, P -31 ) and difficulty awakening (rg = 0.11, P -4 ). Mendelian randomization analyses provided evidence for potential causal effects of difficulty awakening on risk of migraine (OR [95% CI] = 1.37 [1.12-1.68], P = 0.002), and nominal evidence that liability to insomnia symptoms increased the risk of migraine (1.09 [1.02-1.16], P = 0.02). In contrast, there was minimal evidence for an effect of migraine liability on sleep patterns or disturbances.InterpretationThese data support a shared genetic basis between several sleep traits and migraine, and support potential causal effects of difficulty awakening and insomnia symptoms on migraine risk. Treatment of sleep disturbances may therefore be a promising clinical intervention in the management of migraine.

Original publication

DOI

10.1002/acn3.51228

Type

Journal article

Journal

Annals of clinical and translational neurology

Publication Date

12/2020

Volume

7

Pages

2370 - 2380

Addresses

Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts, 02142, USA.

Keywords

International Headache Genetics Consortium, Humans, Sleep Initiation and Maintenance Disorders, Causality, Databases, Factual, Adult, Migraine Disorders, Genome-Wide Association Study, Mendelian Randomization Analysis, Sleep Wake Disorders, United Kingdom